Synthesis of novel β-carbolines with efficient DNA-binding capacity and potent cytotoxicity

A series of water-soluble β-carbolines, bearing a flexible amino side chain, was prepared and evaluated in vitro against a panel of human tumor cell lines. The N9-arylated alkyl substituted β-carbolines represented the most interesting cytotoxic activities, and compound 7b was found to be the most potent antitumor agent with IC50 values lower than 10 μM against eight human tumor cell lines. The results confirmed that the N9-arylated alkyl substituents of β-carboline nucleus played an important role in the modulation of the cytotoxic potencies. In addition, these compounds were found to exhibit significant DNA-binding affinity.

Graphical abstractA series of water-soluble β-carbolines, bearing a flexible amino side chain, has been prepared and evaluated in vitro against a panel of human cell lines. Compound 7b were found to be the most potent compound with IC50 values lower than 10 μM against eight human tumor cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide